NEW YORK (CBS.MW) -- The impending publication of the landmark blueprint of human genetic code in a peer-reviewed scientific journal may have implications for companies in the gene-research business.

It also has implications for investors.

Last June, Celera Genomics (CRA: news, msgs) and scientists from the government-funded Human Genome Project unveiled a rough draft of the genetic code for human life, in what was hailed as one of mankind's greatest scientific accomplishments.

Analysts have been speculating for some time that the publication would appear in one of the journals Science or Nature in late January or February. The paper will be unveiled on Monday and will appear on Science's and Celera's Web sites. Its appearance finally enables researchers to assess the validity of the published paper, which is necessary for all scientific publications. The publication of the human genome is expected to be available in print on Thursday in the journal Nature.

Celera finished the sequencing and assembly of the complete set of genetic material from five different people last year. Its information database is "far more complete and accurate than any other available today," says Eric Schmidt, an analyst at S.G. Cowen.

Gene tally

Winton Gibbons, an analyst at William Blair & Co., believes that Celera's paper will contain an estimate of about 26,000 human genes, substantially lower than the 100,000-gene tally that has been bandied about for months on Wall Street and also in the scientific community.

Gibbons agrees that Celera's data is comprehensive. The gene estimate is based on the company's data, which it has compared with its proprietary sequence of the mouse genome. A mouse's genetic material is very similar to that of a human, which could lend credence to the accuracy of the estimate.

The number of genes, if it is indeed lower, could affect the share prices of a number of companies.

Gibbons says that if the number of genes is less than had been anticipated, the faster the path to medical breakthroughs -- and profitability -- for a number of genomics companies.

Rivals Incyte Genomics(INCY: news, msgs), Affymetrix, (AFFX: news, msgs) and Human Genome Sciences (HGSI: news, msgs) have different estimates of the number of genes that range from 60,000 to more than 100,000.

They aren't the only companies whose fortunes and futures are tied to the "official" tally. There are hundreds of biotech companies that are hoping to capitalize on the genomics revolution.

The publication is also significant for investors. It may enable them to begin evaluating biotechnology companies with greater precision, instead of simply riding a wave.

WASHINGTON, Feb 10 (Reuters) - The scientists who made history last year by discovering the code of the human genomeare starting to break the code, but they are also already looking ahead to what is next.

On Monday, the public effort and a private U.S. company who jointly announced they had the text of the human genetic codeplan to describe what they have been able to read in it.

The announcement is being made under unprecedented security at simultaneous news conferences around the world by bothteams, who want nothing to leak out ahead of time.

They have been both competing and cooperating on the effort, but agree it will be years before they know more than a tinyfraction about what underlies human genetics.

``This is just the very, very beginning,'' Ari Patrinos, who heads the genome sequencing effort at the U.S. Department ofEnergy, said in an interview.

The DoE is helping fund the public team working on the sequencing, which is spread across academic and government labsfrom the Whitehead Institute at the Massachusetts Institute of Technology to the DOE Joint Genome Institute in Walnut Creek,California.

The public effort spreads internationally as well, from the Sanger Center in Cambridge, England, to labs in Germany, France,Japan, China and elsewhere.

Heading the private effort is Rockville, Maryland-based Celera Genomics (NYSE:CRA - news), a company founded in partby scientist Craig Venter, who left the public effort to try and make money at the endeavor.

JUNE ANNOUNCEMENT MADE HEADLINES

Last June, both teams announced they had the full sequence of the human genome -- the collection of nucleotides, known bythe letters A, C, T and G, that make up the ``rungs'' in the ladder-like twists of DNA.

The four letters recombine over and over again, 3.1 billion times, to make up the human genome. This includes the genes, whichform only a fraction of the genome, and other DNA.

A gene itself is the part of this repetitive code that controls a protein -- the basic product of a cell that underlies all biologicalprocesses.

The rest once was called junk, but scientists now believe much of it also plays a very important role, although they are not surewhat.

Many genes are already known such as those that repair cells, those involved in various cancers and the tiny mutations thatcause cystic fibrosis.

But most are not. Patrinos said the amount of code that has to be analyzed is daunting.

``This is still a working draft and we still have about three more years of finishing to do,'' he said. ``What remains to be done isquite difficult.''

But he said even he is surprised that the teams have come so far, so fast.

LONG-TERM PROGRAM

``Those of us in the trenches who have been one way or another involved in the program for 16 years -- we were kind ofdreaming of this day,'' he said.

``What was considered a kooky idea is now viewed as perhaps the most amazing scientific endeavor ever. It's wonderful tosee it in one's lifetime.''

Eric Lander, who heads the sequencing team at the Whitehead Institute, agrees. ``We have climbed to the top of a greatmountain. We are excited and maybe a bit giddy, but what we have seen is a wonderful range of mountains ahead,'' he said in atelephone interview.

Scientists hope that understanding the genome will transform medicine and basic biology.

Although they are coming to understand that it is not a simple matter of one gene, one disease, they hope one day to be able tobetter predict who is at risk of what so they can make changes early, before they develop heart disease or cancer or diabetes.

``I think this is probably the one scientific undertaking people can relate to most because the first and most obvious applicationis in human health,'' Patrinos said.

``And we talk about the Holy Grail here which is gene therapy -- the ability to intervene at genetic level and fix things. We nowuse a hammer when we should be using a fairly miniature instrument.''

As Celera Finishes Genetic Code, Analysts Look for an Encore By Brian Reid

Washington, Feb. 9 (Bloomberg) -- Applera Corp.'s Celera Genomics unit next week will share the results of its 17-month dash to unravel the human genetic code, as it prepares to use that data in a gamble on drugmaking.

Celera, founded as a tracking stock of the company now called Applera, was envisioned as a database powerhouse, decoding the genome with powerful equipment and selling the results to drugmakers.

Now Celera is looking to move far beyond the database business and become a drug developer itself, analysts said, entering a risky but potentially lucrative business.

``Drug discovery is a naturally progression from where they are now,'' said James Reddoch, an analyst at Banc of America. ``It's only natural that they would want to leverage that gene database into products.''

Though Celera has a reputation for speed -- it decoded the human genome years faster than originally thought -- moving the company into drug development may be a slow process.

The company hasn't given specific financial targets, said S.G. Cowen analyst Eric Schmidt, making it difficult to assess when Celera will turn its know-how into drug targets -- and revenue.

``We know where they're going to go . . . but we don't know how they're going to get there,'' said Doug Lind, a Morgan Stanley Dean Witter analyst. ``There's not a lot of meat on the bones in terms of a business model.''

Different Avenues

Still, Lind, who rates Celera shares ``outperform,'' said with the task of deciphering the human genome, the company will be able to use its database to sift out new treatments; the only question is how much time that will take.

Celera and the publicly funded group that decoded the genome will publish their findings in scientific journals next week. The sequence, amounting to about 3 billion letters representing chemicals that make up DNA, will be made available to the academic community on Monday.

The company, which has more than $1 billion in cash and short- term investments, is pursuing a number of strategies. In addition to its database business, which counts more than a half-dozen drugmakers and biotechnology companies as clients, Celera is making a large bet on an emerging field known as proteomics, the study of the body's proteins and how they interact.

The Rockville, Maryland-based company has committed to building a facility devoted to proteomics. With that, it could tease information out of the gene databases and speed the discovery of new drugs. Celera, however, may lag rivals who have already begun trying to leverage genetic and protein information in the search for better pharmaceuticals.

Betting on People

Investors say that Celera's ability to leapfrog other biotechnology companies in drug development rests on its scientists, who include gene-finding superstars like its president, Craig Venter, Nobel laureate Hamilton Smith, and Stephen Hoffman, a well-known vaccine researcher from the U.S. Navy who joined the company last month.

``The bet here is on the people,'' Lind said. ``These are smart people, and they're sitting on a huge asset.''

Hoffman's hire signals a commitment to vaccine development as well, analysts said, and Venter hailed Hoffman's addition as a key to the company's new focus on disease treatment.

Still, the company is expected to rest on the success of its database business for now. Celera's success in selling access to its database helped it generate better-than-expected revenue of $20.3 million in the fiscal second quarter ended Dec. 31.

That business, however, barely supports the company's $2.5 billion market capitalization. The shares soared as high as $276 a year ago, and now trade at about $42.

The human genome, analysts say, is only the beginning for Celera.

``A company the size of Celera is already bigger in terms of expectations than that market can provide for,'' said Schmidt. ``Drug discovery is the topic that everyone wants to talk about.''

LONDON, Feb 11 (Reuters) - Scientists will publish the initial sequence of the human genome on Monday in a breakthroughthat promises to revolutionise the understanding and treatment of diseases.

The sequencing of 3.1 billion letters of DNA show humans are made up of about 30,000-40,000 genes, considerably fewerthan earlier estimates of 60,000-100,000 genes, and only about twice as many as the earthworm and fruitfly.

Scientists say identifying all the genes and what they do will herald a new age in science and medicine, vastly expanding humanknowledge and accelerating the diagnosis and treatment, as well as potential preventions and cures, for disease.

``It is going to revolutionise science and medicine,'' Tim Hubbard of the Sanger Centre in Cambridge, England who worked onthe project, told Reuters.

``Everything about us is in the sequence.''

The Human Genome Project, the publicly funded international collaboration of 20 groups of scientists from the United States,Britain, Japan, France, Germany and China, completed the working draft of the human genetic code in June.

All the information has now been arranged and is published in the scientific journal Nature with a dizzying array of reports,maps and analysis to explain what it all means.

Celera Genomics Inc (NYSE:CRA - news), of Rockville, Maryland, the privately owned company which raced to produce thefirst draft, reported their findings in the journal Science.

EARLIER DIAGNOSIS, DESIGNER DRUGS

The sequence is just the beginning and will not be fully finished for several years but it is already revealing its secrets -- far fewergenes, where they come from, the complexity of proteins and what makes us different from other organisms.

Genes comprise only a tiny fraction of human DNA but they represent the major biological function of the genome. They arealso the most challenging feature to identify in the genome. Ultimately researchers hope to compile a complete list of all humangenes and the proteins they encode to aid scientists in biomedical research.

The biggest initial impact of the human genome is expected to be on drug development, customising drugs to individual geneticprofiles and earlier diagnosis of disease.

Currently there are fewer than 500 targets for all the drugs on the market. Scientists predict the sequencing will increase thatnumber to several thousand, sparking a boom in genomic research in the pharmaceutical industry.

``There are potentially a huge number of targets that can be investigated for potential drugs. There is also the personalisation ofmedicine,'' Hubbard said.

He likened the human genome to an automobile manual used by mechanics to determine what is wrong with a car that isn'trunning properly.

``We're going to provide doctors with much more powerful tools to diagnose exactly what is wrong with somebody.''

SPOT THE DIFFERENCE

The sequence has already allowed scientists to identify more than 1.4 million SNPS, single nucleotide polymorphisms --variations in the three billion letters of the human genetic code.

SNPS are single changes in the arrangement of those letters that make people different. They hold the key to susceptibility toillnesses such as cancer, diabetes and heart disease and individual responses to medication.

By looking at different subsets of the genome of several people and comparing the results, scientists hope to identify specificDNA variations that cause propensity for a certain disease as well as its genetic basis.

The Human Genome Project has moved rapidly since the working draft was announced in June and the scientists have closed anumber of gaps. But they stressed that much remains to be done to produce a finished sequence and the rewards will not bereaped overnight.

``Fulfilling the true promise of the Human Genome Project will be the work of tens of thousands of scientists around the world,both in academia and industry,'' the scientists said in the Nature report.

They also warned that along with its great promise the sequencing has serious legal, ethical and social implications.

``Understanding and wisdom will be required to ensure that these benefits are implemented broadly and equitably,'' they added.

LONDON, Feb 11 (Reuters) - Science passes another milestone with publication on Monday of the first description of thehuman genome but the path to a new era of genomics-based medicine is proving longer and more costly than first thought.

Few doubt that sequencing the 3.1 billion letters in the digital ``recipe book'' that determines all human traits will eventuallytransform healthcare.

Today's medicines are aimed at a total of just 483 biological targets. The mapping of the genome may yield another 5,000 ormore, scientists believe, even if only a minority of the 30-40,000 genes now thought to exist in the human body turn out to be``druggable'' targets.

That promises new medicines and cures for difficult-to-treat conditions like heart disease, Alzheimer's and cancer.

But the immediate impact on the $300-billion-a-year pharmaceuticals industry will be an increase in costs rather than a profitbonanza, according to new research from U.S. investment bank Lehman Brothers and consultants McKinsey.

Ian Smith, an analyst with Lehman in London, said the average cost of bringing a new drug to market, including the cost offailures, was likely to double from $800 million in 2000 to $1.6 billion in 2005 before falling to $1 billion in 2010.

The reason is simple -- in the next few years the drugs industry will be working on a much higher percentage of unprecedenteddrug targets which, by definition, will have a higher failure rate than conventional drugs following in the footsteps of establishedproducts.

Those expecting a near-term explosion in drug industry productivity and a surge in new drug approvals are likely to bedisappointed.

``Genomics and ancillary technologies will lead to many more opportunities for drug discovery and development, but we areheading for a period of indigestion as the industry learns how to move from genes to validated drug targets,'' Smith said.

STRETCHED TIMELINES

A year ago, genomics was one of the hottest areas for investors looking for the next ``big idea'' in technology in the dying daysof the dot.com bubble.

Since then, the market has come down to earth with bump. Shares in Celera (NYSE:CRA - news), the genomics firm foundedby scientific maverick Craig Venter that spearheaded the mapping of the genome, hit a high of $275 last February but are nowtrading at around $45.

Iceland's deCODE Genetics (NasdaqNM:DCGN - news), founded to mine the country's unique genetic heritage, havetumbled from $30 in August to around $9 now.

``Over the long-term -- and I'm talking decades -- the human genome will change society, let alone healthcare. What isforgotten is the huge timelines involved. From a single gene discovery it can take 10 years to get a pharmaceutical and the risksof failure in clinical trials have not been lowered.''

WORK IN PROGRESS

Work on drugs focused on specific genes has been going on since the early 1990s, even without knowledge of the wholegenome. But it is only now starting to yield results.

Human Genome Sciences Inc (NasdaqNM:HGSI - news) and Cambridge Antibody Technology (quote from Yahoo! UK &Ireland: CAT.L), for example, expect to start clinical trials by the end of the year on a genomics-derived antibody drugdesigned to help people suffering certain immune system defects.

But mainstream drug companies have yet to derive any small molecule drugs from their genomics efforts. Small moleculeproducts, as opposed to protein drugs, are the ``holy grail'' of drug discovery since they can been given as tablets rather thanby injection.

Francis Collins, head of the National Human Genome Research Institute (NHGRI) which is leading the publicly funded HumanGenome Project, has a vision of designer drugs based on genomics research which will tackle the root cause, rather than thesymptoms, of many serious diseases -- sometime after 2020.

Ten years before that, science should have produced accurate predictive tests for at least a dozen common diseases in whichan individual's genes play a part -- such as diabetes and heart disease -- allowing doctors to target drug prescriptions far moreaccurately.

Bill Castell, chief executive of gene technology company Nycomed Amersham (quote from Yahoo! UK & Ireland: NAM.L), sees aparallel with the start of the biotechnology industry, based in recombinant DNA, 20 years ago. That industry has only reallystarted to make significant money since 1996.

``Genomics will have a very significant impact on healthcare and will lead to a whole new era of personalised medicine -- butit's not going to happen overnight,'' he said.

WASHINGTON, Feb 11 (Reuters) - The first in-depth look at the human genetic code has revealed much less thananticipated -- about half to a third the number of expected genes, scientists will announce on Monday.

They said their findings so far made it clear that far from being a blueprint, the human genetic code was only a guidepost. Thetrue directions for what makes a human being lie not in letters of code but in what the body does with that code.

They have found a few interesting tidbits.

Most of the variation -- the mutations that underlie evolution and bring gradual change -- is on the Y chromosome. That meansmen are responsible for most mutations, because only men have a Y chromosome.

They have also confirmed that there is no genetic basis for what people describe as race, and found only a few small differencesset one person apart from another.

``You and I differ by 2.1 million genetic letters from each other,'' Craig Venter, chief scientific officer at Celera Genomics Inc.(NYSE:CRA - news), which carried out one of the two studies being published, said in a telephone interview.

``Probably only a few thousand of those differences account for the biological differences between us, which means we all areessentially identical twins -- even more than I thought.''

RACE IS 'NOT A SCIENTIFIC CONCEPT'

Celera used DNA from five volunteers -- three women and two men, ethnically African-American, Chinese, Hispanic andwhite.

``You can clearly tell the females from the males because of the X and Y chromosomes, but race is not a scientific concept,''Venter said.

The future, both teams of researchers say, lies in understanding the proteins that make up people and not so much the genesthat control production of the proteins. This infant scientific field is known as proteomics.

``There are about 30,000 to 40,000 protein-coding genes in the human genome -- only about twice as many as in worm orfly,'' members of the International Human Genome Sequencing Consortium, the public effort, wrote in their report.

``However, the genes are more complex, with more alternative splicing generating a larger number of protein products,'' theyadded in their report, to be published in next week's issue of the journal Nature.

In other words, the proteins for which genes code can be mixed and matched to make even more, just as the primary colors --yellow, red and blue -- can be mixed to make a myriad of colors.

Rockville, Maryland-based Celera finds a similar number in its own, separate analysis, published in the journal Science --somewhere between 26,383 and 39,114.

Originally, scientists thought there were about 100,000 human genes, but in recent years revised that downward to between60,000 and 80,000.

The two studies were to be released on Monday as part of a carefully coordinated and controlled announcement. But BritishSunday newspapers broke the careful embargo, so the material was released on Saturday night.

Researchers said they were surprised to find so few genes.

``On the one hand, this is spectacular news because it means we have only a third as many proteins to understand,'' EricLander, head of genome sequencing at the Whitehead Institute at the Massachusetts Institute of Technology (MIT), said in atelephone interview.

``On the other hand, we may feel we have set ourselves a larger problem. Although there are fewer components, they fittogether in more complex ways,'' added Lander, whose lab did much of the work in the public effort.

``If anyone found the basis for the pride of our species in the number of genes we had, they may have to rethink it.''

Venter agrees. ``There are only a few hundred genes that we have in the human genome that are not in the mouse genome,'' hesaid.

IT'S NOT A BLUEPRINT

``In fact, what has been said about the human genome, that it is the blueprint for humans, it's not true. We don't think blueprintis the right metaphor.''

Both teams had announced jointly last June that they had sequenced the human genome -- 3.1 billion base pairs, the rungs thatmake up the ladder-like double helix of DNA. But all they had was a repetitive readout of A's, C's, T's and G's, the nucleotidesthat pair up.

They did not know what that code said.

Eight months later, they have done the first analysis and have found what they believe to be a history of human evolution. Thechanges that made humans a little different from other animals had been preserved, Lander said.

``In June, maybe people thought we had this big pile of letters and it was all stuff,'' Lander said. ``But I don't know if peoplerealize that we just found the world's greatest history book. We are going to be up every night reading tales from the genome.It's so cool.''

By Maggie Fox, Health and Science Correspondent WASHINGTON, Feb 11 (Reuters) - Our future may not lie inour genes, after all. Two separate teams of researchers will report on Mondaythat they have taken the first in-depth look at the humangenetic code and found about half what they expected to find.Instead of 60,000 to 80,000 genes, we have only 30,000 to40,000. Both teams agree this means that, in humans anyway, it isproteins that matter -- much more so than genes. "Those who are looking for forgiveness of responsibilityfor their own lives in the genetic code will be verydisappointed," Craig Venter, president and chief scientificofficer of Celera Genomics Inc. <CRA.N>, the private companythat did one of the studies, said in a telephone interview. The human body, it seems, is set up to adapt to itsenvironment, by cutting up and recombining the protein"products" of genes to make a protein suitable for thecircumstance. Each gene makes one protein -- this is the basic functionof any cell. Researchers had known that proteins often have tobe sliced in a certain way, a process known as cleaving, beforethey do anything useful. "Most of biology happens at the protein level, not the DNAlevel," Venter said. What had not been known was the degree to which this istrue. The implications could be profound for medical science,which had hoped to find easy genetic answers to disease and tohow people will respond to drugs.

GENE PATENTS "IRRELEVANT" "This shows how irrelevant human gene patents are," Ventersaid. "The drug industry has been saying 'one gene, one patent,one drug'. But the uses for this approach can be counted onfingers." Both teams, who publish their findings in the rivalscientific journals Nature and Science, are fairly certain. "Given all the tools that we threw at this problem, wecannot imagine that there are many more genes," Mark Adams,vice president at Celera, told a briefing for journalists. "We only have twice as many genes as a fruit fly. But weare more complex. We can think more thoughts. Our bodies can domore things." Humans have 3.1 billion base pairs of genetic code. A basepair is a joining of two nucleotides -- known by the lettersA,C,T and G. These repeat over and over in various combinationsto make amino acids, which in turn combine to make proteins. "The size of the genome, the number of base pairs, isirrelevant to biology," Venter said. "Corn has the same number of genes as humans. The lilyplant has 91 billion pairs of genetic code." Each protein equals a gene, but there are long stretches ofbase pairs that do not code for proteins, areas once known asjunk DNA. These areas may help control genes. Only just over one percent of the genome is accounted forby protein-expressing genes. Venter says all this means genes,per se, are just a small part of the story. "Genes don't determine whether you get colon cancer," hesaid. "They determine whether you have an increased risk forcolon cancer. We get a set of probabilities from our geneticcode, a sort of range of parameters that we can work within."

KIND OF HUMBLING "It's kind of humbling, isn't it?" Ari Patrinos of the U.S.Department of Energy, which funded much of the public effort,said in a telephone interview. "There are very, very few few traits or diseases that aremonogenic (caused by a single gene). It's been an emergingconsciousness over the past five years, and the recognitionthat ... our genes don't control everything." It also means the so-called "junk DNA" may be moreimportant than at first thought. "We just don't know. We don't call it junk," Venter said. Eric Lander, who heads the genome lab at MassachusettsInstitute of Technology's Whitehead Institute, said the"alleged junk" provides a history. "The junk is amazing. Every piece of junk in the genomerepresents a transposable element," he said. In other words, it is genetic material that people got fromelsewhere, such as from bacteria the readily lend their DNAout, retroviruses that inject their genetic information intocells, or by a cut-and-paste process done by genetic elementsknown as transposons. If it stayed there through generations,it might do something useful. Lander thinks some of the "junk" may help regulate genes --a role that is more important the fewer genes there are. And some of the genes are borrowed, too. Lander said histeam found that the gene for monoamine oxidase, an enzymeimplicated in depression and targeted by drugs called MAOinhibitors, came from bacteria.

NOT EVERYONE AGREES Not everyone agrees with all the conclusions. "We know that they have missed very, very many genes thatwe know exist," William Haseltine, head of Rockville,Maryland-based Human Genome Sciences Inc. <HGSI.O>, said in atelephone interview. "They have missed at least half the genes, maybe more,"added Haseltine, whose company holds more than 100 genepatents. "They have no medical discovery and they only found athird of the genes. That's a bore." Haseltine, whose company looks for "expressed" genes --those that actually make a protein -- by using bits of DNAcalled expressed sequence tags (ESTs), says he believes thereare 120,000 human genes. Another company that says it has explored the genome, PaloAlto, California-based Incyte Pharmaceuticals Inc.<INCY.O>,maintains there are 140,000. (( -- Washington newsroom 202 898 8300, fax 202 898 8383,e-mail washington.bureau.newsroom@reuters.com)) REUTERS*** end of story ***

Genome Analysis Shows Humans Survive on Low Number of Genes-New York Times 2/11/01

By NICHOLAS WADE

Opening a new era in human biology and medicine, two rival teams of scientists this week present their first interpretations of the human genome, the set of DNA-encoded instructions that specify a person.

The two teams report in articles to be published on Thursday and Friday that there are far fewer human genes than thought — probably a mere 30,000 or so — only a third more than those found in the roundworm.

One team, Celera Genomics, has compiled a parts list of the proteins needed to make a person. The other team, a publicly funded consortium, has traced the history of how the "junk" regions of the genome accumulated and has found that small elements of the junk may play a useful role. They also discovered that human genes have been derived directly from bacteria.

The two teams announced last June that they had assembled the human genome, but it has taken them until now to analyze their findings.

The interpretation of the genome — identifying the genes, their functions and controls, and how they relate to human physiology and disease — is expected in time to revolutionize medicine by clarifying the mechanism of many diseases and generating new tests and treatments.

Physically, the genome is minuscule — two copies of it are packed into the nucleus of every ordinary human cell, each one of which is about a fifth the size of the smallest speck of dust the eye can see. But the genome is vast in terms of its informational content. Composed of chemical symbols designated by a four-letter alphabet of A's, T's, C's, and G's, the human genome is some 3.2 billion letters in length. If printed in standard type, it would cover 75,490 pages of this newspaper.

The enormous task of decoding the genomic message began in 1990 and is now substantially complete, although both teams' versions of the genome are riddled with gaps.

With so much effort and scientific glory at stake, members of each team remain highly critical of the other's approach, believing that their own strategy for decoding the genome is likely to produce the better and more accurate version. Since last June, however, both have been muting criticism and observing a limited truce. The pact called for a joint announcement, made at the White House on June 26 last year, that each side had finished assembling its version of the genome, and for joint publication of their findings, which is occurring later this week.

The joint publication, however, is about as separate as a union could be, with each side's articles appearing in rival scientific journals issued on different sides of the Atlantic. The findings were to be announced tomorrow, but the embargo was lifted by the two journals after The Observer of London broke it.

One team is a consortium of academic centers, mostly in the United States and Britain but with members in France, Germany, China and Japan. The consortium is financed largely by the National Institutes of Health and the Wellcome Trust of London. Its version of the human genome is described in a 62-page article in Nature, based in London. The principal author is Dr. Eric Lander of the Whitehead Institute in Cambridge, Mass.

The other team is led by Dr. J. Craig Venter, president of Celera Genomics in Rockville, Md. Its report appears in a 48-page article in Science, based in Washington.

Despite the two team's many differences, they largely agree on their findings about the human genome. Theirs is the first overall look at a genetic document of extraordinary strangeness and complexity. No one expected it to be comprehensible at first glance and the two teams have so far mapped only the principal features of its terrain.

Genome Analysis Shows Humans Survive on Low Number of Genes

(Page 2 of 3)

Their principal discovery is how few human genes there seem to be. Textbooks have long pegged the number of human genes at around 100,000, but with the sequence of human DNA units in hand the two teams have found far fewer than expected. Dr. Venter says he has identified 26,588 protein-coding genes for sure and another 12,000 possible genes. The consortium says there are 30,000 to 40,000 human genes. Both sides prefer the lower end of their range, since their methods of gene discovery tend to predict more genes than they believe exist.

The low number of human genes — say 30,000 — can be seen as good for medicine because it means there are fewer genes to understand.

The impact on human pride is another matter. Of the only two other animal genomes sequenced so far, the roundworm has 19,000 genes and the fruit fly, also a standard laboratory organism, 13,000. Both teams devote part of their huge articles to discussing how it is that humans are more complicated than simple invertebrate animals even though they possess not that many more genes.

Despite these face-saving efforts, human self-esteem may be in for further blows as genome analysis progresses. Dr. Venter said he could find only 300 human genes that had no recognizable counterpart in the mouse. The mouse, though a fellow mammal, last shared a common ancestor with people 100 million years ago, time in which many more genetic differences might have been expected to develop.

Given the minor difference between man and mouse, Dr. Venter said he expected the chimpanzee, which parted company from the human line only five million years ago, to have an almost identical set of genes as people but to possess variant forms of these genes.

The consortium, taking its own jab at anthropocentric pomp, identified 113 human genes, and possibly scores more, that have been acquired directly from bacteria.

In the journal articles, the two sides also sketch out major features of the genome's architecture, of which genes are only a small part. More than half the genome consists of repetitive DNA that has no genetic meaning. Much of the repetitive DNA is formed by a couple of rogue genes that millions of years ago learned to copy and insert themselves into new sites in the genome. Because mutations clock up in these repeated segments at a fairly regular rate, their origins can be dated.

The consortium has found that the main families of repetitive DNA fell extinct long ago and no longer add clutter to the genome. But one family is still active, and since its members are often found near active genes they may benefit the genome in some way.

Both teams' versions of the genome now seem to be in a good enough state to be of great use to biologists. The consortium's genome is available for free and Celera's through subscription. But Celera provides extra services, such as the ability to compare the human genome sequence with that of the mouse. Mouse DNA has retained a very similar sequence to human DNA both in its genes and in the DNA regions that control the activity of genes, but has diverged through mutation in all the nonessential parts of the genome. Laying mouse DNA on top of human DNA shows at a glance which regions evolution has thought worth conserving.

The consortium, however, is also working on the mouse genome and intends to put that and other important tools for interpreting the human genome in the public domain.

Experts are likely to debate which team's method for sequencing the human genome is better. Dr. Venter's article includes a comparison chart that shows that the consortium's version of the genome has many more gaps than Celera's and that the gaps are larger. But in an interview Dr. Venter complimented the consortium's efforts. "We are really impressed at how good the public paper is, given their input data," he said.

Genome Analysis Shows Humans Survive on Low Number of Genes

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But Dr. Lander said Celera's strategy was a grand experiment that failed because it produced more than 100,000 assembled pieces that could not be anchored to the genome sequence. Dr. Mark Adams of Celera said that the statement was inaccurate and that the company had assembled more than 95 percent of the genome into 2,845 large pieces that were well anchored to the genome.

Despite their different strategies, both sides borrowed heavily from the other. Dr. Venter used not only the snippets of DNA decoded by the consortium but also important information about their position generated by Dr. Robert H. Waterston of Washington University in St. Louis. The consortium belatedly copied two of Dr. Venter's innovations, a clever method of linking DNA sequence data by "paired-end reads," and reliance on heavy-duty computing to assemble data. The consortium had not prepared an assembly program, even though much of the analysis in the report depends on it, until a graduate student at the University of California at Santa Clara, James Kent, stepped in and wrote one for them at the last minute.

The rivalry between the two sides takes many petty forms — speaking time for each side at a news conference to be held tomorrow was negotiated to the minute, and academic scientists including Dr. Lander tried strenuously to prevent Science from publishing Celera's article except under terms unacceptable to Dr. Venter. But the competition has proved enormously beneficial overall. The consortium was on a leisurely track to finish the genome by 2005 until Dr. Venter jumped into the race in May 1998, saying he would complete the genome by 2000.

"I think the publicly funded group has brought off something extraordinary," said Dr. Donald Kennedy, editor of Science and former president of Stanford University. "Imagine trying to do this job in a number of places with academic scientists — it's like herding cats. They deserve all kinds of credit, but so does Venter and Celera. There is no doubt the world is getting this well before it otherwise would have if Venter had not entered the race."

The closeness of the finish has now become apparent. Dr. Venter said in his article that he completed his first assembly of the human genome on June 25, just the day before. Mr. Kent completed his first assembly of the consortium's data on June 22, just three days before Celera's.

Both sides have in substantial measure achieved their goals. Celera went from a concept to building a new plant from scratch to completed genome sequence in just 25 months, despite the predictions of the consortium's experts that its DNA sequencing strategy was bound to fail. "This is something I felt I had been driving for for a decade," Dr. Venter said last week, in commenting on his decision to place his name first on the Celera report's list of authors. "No small amount of this was the politics and psychology of being to stay with this and stick with it. If there was any way to stop this, it was tried, down to the end of trying to block our paper being published in Science. If we weren't resistant and somewhat defiant this never would have gotten done."

The consortium's goal was to place the human genome in the public domain for unfettered use by the world's biologists, and it has now done so four years ahead of its original schedule. The architects both of this policy and the DNA sequencing strategy were Dr. John Sulston of the Sanger Centre near Cambridge, England, and Dr. Waterston. Their centers completed roughly a quarter each of the genome sequence, and Dr. Lander's center at the Whitehead Institute did another quarter. Dr. Lander was also chairman of the group that analyzed the completed genome sequence. The consortium was led by Dr. Francis S. Collins of the National Institutes of Health.

Both teams believe that the sequencing and interpretation of the human genome is a historic event and expressed pride in their accomplishments. But both groups expressed humility at the minute steps they have so far taken in exploring the human genome's vast repository of knowledge.

"In principle," the consortium's biologists concluded in their report, "the string of genetic bits holds long-sought secrets of human development, physiology and medicine. In practice, our ability to transform such knowledge into understanding remains woefully inadequate."

Dr. Venter said simply that the effort to sequence and interpret the human genome had been "mentally exhausting, in part because we are not mentally equipped to absorb all this."

"We feel like midgets describing the universe and we can't comprehend it all," he added.

i highlight this bit from the aboveBoth teams believe that the sequencing and interpretation of the humangenome is a historic event and expressed pride in their accomplishments.But both groups expressed humility at the minute steps they have so fartaken in exploring the human genome's vast repository of knowledge.

"He represented his idea as a revolutionary approach and that the public effort was too dumb to recognize that it works. . . . But the whole-genome approach failed," said Philip Green, a specialist in computer-based DNA analysis at the University of Washington in Seattle, who is not a member of either team.